Hair loss prevention

ABSTRACT

Compositions to prevent or reduce hair loss, allowing the body to maintain normal, healthy hair growth, comprising a penetration enhancer together with a testosterone blocker or a vascular enhancer, or both.

BACKGROUND

[0001] My invention relates to preparations useful for maintainingnormal, healthy hair bulb function, for preventing hair loss, and formedically treating androgenic alopecia and like dermatological diseases.I will first review pertinent hair biology, then discuss prior artteachings in the field, and then describe my invention.

[0002] Hair Biology

[0003] Hair bulbs are responsible for normal, healthy hair growth andretention. Hair bulbs are located in the skin, about {fraction (3/16)}of an inch below the skin surface. They are located just above the fattylayer at the very lower most position of the skin.

[0004] The majority of facial and body hair growth is stimulated byandrogens. However, the growth of scalp hair has been shown, ingenetically programmed individuals, to be inhibited by5α-dihydrotestosterone (“DHT”) in individuals who exhibit a hereditarypre-disposition to baldness. Ebling, Dermatol. Clin. S. 467 (1987);Lucky, 4 Biochem. Soc. Transc. 597 (1988); Brodland et al., 47 Cutis 173(1991). DHT is produced by reducing testosterone with a 5α-reductaseenzyme. The phenotypic expression of baldness does not occur in theabsence of testosterone. Androgenic alopecia or common baldnessrepresents 99 percent of all cases of hair loss. Broadland, id.

[0005] The mechanism through which androgens regulate the biology ofhair is by modulating the hair growth cycle. Ebling, 4 Biochem. Soc.Trans. 597; Bergfield et al., 5 Dermatol. Clin. 491. The effect of DHTon hair growth appears to be related to local rather than systemiclevels of the hormone. This is because the capacity of scalp skin frombalding individuals to convert testosterone (“T”) to DHT is greater thanthat observed in the scalp of non-balding individuals. Lucky, supra;Schweikert et al., 38 J. Clin. Endocrinol. Metab. 811.

[0006] To prevent hair loss, maintain the health of hair bulbs, or totreat baldness, several compositions are known in the art. We discussthem now.

[0007] Hair Loss Prevention

[0008] Hair loss prevention preparations are known in the art. Theseinclude natural product preparations, biological products, vasculartoners and testosterone blockers. Several prior art compositions arediscussed in the accompanying Petition To Make Special and itsaccompanying references, the contents of which are incorporated hereinby reference.

[0009] Natural Products. Several inventors disclose naturalcompositions. Casero, U.S. Pat. No. 5,340,579, discloses a compositioncomprising (a) mucopolysaccharides, (b) human umbilical cord extract,(c) tetrahydrofurfuryl nicotinate, and (d) pharmaceutically andcosmetically acceptable excipients. Buck, U.S. Pat. Nos. 5,512,275 and5,609,858, discloses a formulation for the treatment of androgenicalopecia, comprising liquor carbonis detergens in combination withspirits of camphor, castor oil, isopropyl alcohol. Chizick et al., U.S.Pat. No. 5,972,345, discloses a combination of saw palmetto extract,African pygeum extract, and stinging nettle extract.

[0010] Biological Products. Hoke, U.S. Pat. No. 5,994,319, disclosesusing genetic material as a anti alopecia therapeutic. Hoke proposesusing anti-sense oligonucleotides targeting 5-α reductases inconjunction with other hair growth enhancers. Tien, U.S. Pat. No.5,574,011, discloses the use of a class of LHRH analogs for treatingmale pattern baldness. Messenger, U.S. Pat. No. 6,020,327, disclosesadministering aromatase inhibitors to treat hair loss. Liao et al., U.S.Pat. Nos. 5,422,371 and 5,605,929, discloses a class of anti-androgeniccompounds.

[0011] Vascular Toners. Several organic chemicals are known to affectthe hair growth and hair retention cycle. These include minoxidil. Irefer to minoxidil and similar kinds of compounds as “vascular toners,”because they are believed to be effective due to their impact on localblood circulation.

[0012] Minoxidil has been shown to stimulate hair growth or inhibit theloss of hair in a number of patients beginning to develop androgenicalopecia. Minoxidil is the generic name for 6-(1-piperidinyl)-2,4-pyrimidinediamaine 3-oxide. Its preparation is disclosed in Anthony,W. C. et al., U.S. Pat. No. 3,382,247 (1968); McCall, J. M., et al., 40J. Organic Chem. 3304 (1975); Gorecki, D. K. J., 17 Analytical Profilesof Drug Substances 185 (Academic Press, New York 1988). It is moresoluble (by weight minoxidil/volume of solvent) in non-polar solventsthan polar ones (75 mg/mi in propylene glycol; 44 mg/ml in methanol; 6.5in dimethyl sulfoxide; 2.2 mg/ml water).

[0013] Minoxidil is medically classified as an anti-hypertensive. Itaffects heart rate and rhythm. It has thus been used in an oralformulation as a cardiac drug. Andersson, O., 205 Acta Med. Scand. 213(1979); Moser, M., 26 Advan. Cardiol. 38 (1979). Over dosage may createcardiac arrhythmias or other adverse side effects. See e.g., Carlson, E.S., 39 Toxicol. Applied Pharmacol. 1 (1977).

[0014] Minoxidil is also medically classified as an anti-alopecia agent.Its efficacy in treating early male pattern baldness has been describedin numerous published articles. E.g., Olsen, F. A. et al., 13 J. Am.Acad. Dermatol. 185 (1985); Novak, E., 24 Int. J. Dermatol. 82 (1982).Its limited percutaneous absorption and secretion is described in Franz,J. T., 121 Arch. Dermatol. 203 (1985).

[0015] The mechanism by which minoxidil alters the hair growth cycle isuncertain, It is thought to act by increasing vascular circulation tothe hair follicle. It is known that minoxidil effectiveness is morepronounced in scalp areas which are more vascular.

[0016] Topical minoxidil is know to have certain shortcomings. It iseffective in only about eight percent of adult male users. It produces“lanugo,” or baby-type, hair which is relatively thin. Further, andperhaps most significantly, after approximately 30 months of continuoususe, minoxidil shows a sharp drop in effectiveness. After about thirtymonths of use, about half of the new hair growth falls out. Thus, whilethe user has somewhat more hair than originally, the user has less hairthan originally seen.

[0017] Testosterone Inhibitors. Inhibitors of steroid metabolism,particularly those that inhibit the conversion of testosterone todihydro testosterone, have shown effects on hair cycles, includinginhibition of hair loss. One class of enzymes targeted by theseinhibitors are the steroid 5-α reductases.

[0018] Certain 5α-reductase inhibitors have been shown to inhibit hairloss. For example, stump-tail macaque monkeys treated with the 5α-reductase inhibitor 17b-N,N,-dimethylcarbamoyl-4-methyl-4-aza-5aandrostan-3-one undergo significantly less age related hair loss thanuntreated monkeys. Rittmaster et al., 65 J. Clin. Endocrinol. Metab. 188(1987). Similarly, finasteride, a 5α-reductase inhibitor, miniaturizesscalp hair follicles, reversing the balding process. “Merck's PropeciaShows Promise In Hair Loss,” Marketletter (Mar. 31, 1997). Theseinhibitors are thought to work by inhibiting the reduction oftestosterone to DHT, as DHT is considered to be the more active form.The use of a combination of finasteride and minoxidil demonstrated that,in combination, these two drugs increased the rate of hair growth whencompared to either compound administered alone. Diani, 74 J. Clin.Endocrino. Metabol. 345.

[0019] Minoxidil used in conjunction with effectors of steroidmetabolism, leads to enhanced hair growth and decreased rates of hairloss.

[0020] Testosterone blockers are known in the art (I use the term“testosterone blocker” to denote a competitive antiandrogen whichinhibits the binding of testosterone or DHT onto its cell surfacebinding site, rather than a compound which is used to inhibit thereduction of testosterone into DHT.). Also known is their usesystemically (orally or intravenously). As systemic therapeutics, theyare known in the art as having a key shortfall: their long term efficacyis compromised by their blocking of the androgenic feedback inhibitionof gonadotropin secretion. This interference results in elevatedgonadotropin secretion, which in turn increases testicular secretion oftestosterone. The higher level of testosterone eventually overcomes theaction of the antiandrogen. Liao, supra, at col. 3, lines 16-31.

[0021] Thus, what is needed in the art is a safe and effective way tomaintain both the healthy function of hair bulbs, and the health ofexisting hair, that avoids the shortfalls seen in the prior art.

SUMMARY

[0022] I have invented a kind of hair loss prevention composition. Myinvention is a new combination of already known types of compounds. Myinvention can be used either cosmetically (to maintain healthy hairgrowth) or pharmaceutically (to treat a medical condition). It can bemade using components already known in the art, allowing one to enjoythe predictability of use available with these old compounds. Myinvention is flexible enough, however, to also allow one to substitutenewly-discovered compounds substantially equivalent to the already knowncompounds. Thus, my invention can be adapted to allow the user to usethe safest, most effective components then available.

[0023] I have found that certain compounds have greatly improvedeffectiveness—achieving ten times the benefit, or an entire order ofmagnitude—if combined with a skin penetration enhancer. The penetrationenhancer delivers these compounds to the hair bulb, where the compoundsare most needed.

[0024] I have thus found that testosterone blockers, if appliedtopically (rather than systemically administered), are effective inpreventing hair loss, and if used in conjunction with a dermalpenetration enhancer. Such topical use avoids precipitating the systemicincrease in testosterone production seen with oral administration, byminimizing systemic interference with normal gonadotropin secretion. Ihave also found that vascular toners, if applied topically inconjunction with a dermal penetration enhancer, work much better.

DETAILED DESCRIPTION

[0025] My invention includes a skin penetration enhancer used togetherwith a testosterone blocker or a vascular enhancer, or both. I firstdiscuss each component individually, and then discuss the combinationsof these components that I have found most acceptable.

[0026] Penetration Enhancers

[0027] You can use a variety of skin penetration enhancers to makecompositions that work as I intend. Penetration enhancers and skinpenetrating formulations are known in the art. These include the varietyof formulations used from time to time for both psoriasis treatmentpharmaceuticals, and psoriasis prevention nutritional supplements andcosmetics.

[0028] The penetration enhancer (or penetration agent) should beaccepted for human use by relevant government agencies. Thus, dimethylsulfoxide, while within the scope of the claims, is not a preferredpenetration enhancer where that compound is not approved for humantopical use. The penetration enhancer should not chemically react withany other ingredient to impair or alter the composition's stability andshelf life. Thus, one should examine the possible reactivity of a givenpenetration enhancer with a given testosterone blocker or vasculartoner.

[0029] The penetration agent should be cosmetically acceptable. Thus,while I have tested dimethyl acetate, I do not favor it. While it iswithin the scope of the claims, it is a weak penetration enhancer. Thus,one needs to use a lot of it. In these high amounts, it smells bad. Incontrast, methyl acetate is odorless, and I have tested and found itacceptable.

[0030] Several inventors disclose liposome technology to delivercosmetic and dermatology materials. See, for example, Lishko et al.,U.S. Pat. No. 5,753,263, discloses using liposomes to selectivelydeliver a composition to hair follicles. Liposomes are made of fattymaterial, and are suitable for delivering homogenous types of materials.As such, it may be difficult for a liposome to in fact work with acombination of a polar compound (like a minoxidil vascular toner) and anon-polar compound (such as a progesterone testosterone blocker). I thusdo not consider liposome technology within the scope of the term“penetration enhancer” in this patent.

[0031] Vascular Toners

[0032] My invention works with a variety of vascular toners. One canmake compositions within the scope of my invention with minoxidilanalogs or derivatives, or with other anti-alopecia agents, such asdiphencyprone, which work in a similar way, by improving local bloodflow to the affected hair bulbs. Because it has such a broad volume ofuse and scientific study, I prefer to use minoxidil. I thus use it as anexample throughout this specification.

[0033] A vascular toner, if used to maintain healthy function of hairbulbs, must be delivered to the small blood vessels feeding the hairbulbs. I have thus found that the effectiveness of the vascular toner isgreatly improved if it is topically applied along with a penetrationenhancer This allows the vascular toner to act locally.

[0034] The vascular toner must be carefully titrated against thepenetration enhancer. For example, for a given concentration ofminoxidil, one needs to use the penetration enhancer in the appropriateconcentration. If a given penetration enhancer is used in a too highconcentration, the minoxidil may penetrate through the skin and reachthe systemic blood circulation. It can there, if present in sufficientamount, cause side effects as seen by taking oral minoxidil. Thus, it isnecessary to adjust the amounts of penetration enhancer and vasculartoner, depending on the concentration and specific identity of theenhancer and the toner.

[0035] Adding a penetration enhancer to the vascular toner appears tofundamentally change the biological mechanism by which the vasculartoner works. This is shown by the qualitatively different results seenbetween minoxidil and my compounds. The two products produce differenttypes of hair, and for different time periods.

[0036] Minoxidil without a penetration enhancer (as available inROGAINE™ topical minoxidil U.S.P.) produces a different kind of hairthan does minoxidil used with a penetration enhancer. It is known in theart that topical minoxidil without a penetration enhancer (as iscommercially available in ROGAINE (TM) topical minoxidil U.S.P.,commercially available from Pharmacia & Upjohn Inc., Bridgewater, N.J.)results in thin, baby-like, temporary hair, called “lanugo” hair. I havefound that my compounds, by contrast, result in good, coarse, “terminal”hair, hair which is normal, permanent adult hair.

[0037] This indicates that minoxidil without and with penetrationenhancer may act on different types of hair bulbs, or produce differentresponses from the same hair bulbs. Minoxidil without enhancer is onlyweakly soluble in polar solvents. See supra. It thus has difficultydiffusing to the deeply located hair bulbs (roots) which are locatedjust above the deep fat layer. Minoxidil without enhancer may thusaffect only hair bulbs located close to the skin surface, or located ina less fatty skin layer, or hair bulbs most sensitive to changes inblood flow. Alternatively, it may affect the same hair bulbs, but withsuch weak or attenuated effect that the hair bulbs produce a differenttype of hair.

[0038] In contrast, my compounds produce normal, terminal hair. Thisindicates that my compounds act directly on the mature, adult hair bulbsresponsible for terminal hair growth.

[0039] Further, it is known in the art that minoxidil users experience asudden drop in hair thickness after about thirty months of usage. I thushave sought the time at which my compounds have a sudden drop ineffectiveness. Surprisingly, I have found that my compounds apparentlydo not lose effectiveness at all, even after using them forsubstantially greater than thirty months. This confirms that while mycompounds appear to simply restore or preserve normal hair bulbfunction, the prior art compositions do not restore normal hair bulbfunction, but actually provoke an abnormal function—the growth by anadult of baby like, temporary hair. That this function is abnormal isconfirmed by its drop in effectiveness after thirty months; such a dropin efficacy indicates a “tolerance” acquired against-the intervention,rather than the maintenance of a permanent, healthy state.

[0040] This indicates that the physiological mechanisms and biomedicalpathways of the two preparations are different. Minoxidil alone, in theconcentrations typically used, may actually temporarily alter a normaladult body function (causing the adult body to temporarily produceinfant hair). In contrast, my invention simply maintains the normalfunction of the healthy adult body hair bulb, allowing it to continue toproduce normal adult hair as long as the compound is used.

[0041] I have also found that the effect of the formulations depends onlocation of administration. Using the specific formulations disclosedhere, I have observed decreases in hair loss, and a consequentstatistically significant increase in the amount of healthy mature hair,after 4.0-4.5 months on the frontal scalp. On the crown and back of thehead, by contrast, I have observed statistically significant resultsafter 4.5-5.0 months.

[0042] The frontal scalp may react faster because it enjoys greatervascularization and blood flow than the other parts of the scalp.

[0043] Testosterone Blocker

[0044] My invention works with a variety of testosterone blockers. Iprefer to use a blocker already approved for human use by the UnitedStates Food & Drug Administration, as these types of testosteroneblockers, if used in pharmaceutical (as opposed to cosmetic) versions ofmy invention, do not need to undergo as lengthy and expensive a processto verify their safety and efficacy as used in pharmaceutical products.Examples include flutamide, cyproterone acetate, spironolactone,progesterone, or analogs or derivatives of any of these (e.g.,17-hydroxy-16-methylene-Δ⁶-progesterone, 17α-hydroxyprogesterone).

[0045] I have found several surprising things about testosteroneblockers. First, they are not actually necessary for my invention towork; minoxidil alone is effective on 8% of patients, while the sameamount of minoxidil administered with the proper amount of a penetrationenhancer is effective on 35% of patients. Second, testosterone blockersadded to such a mix are synergistically beneficial, increasing theefficacy from 35% to 85% of patients.

[0046] One testosterone blockier is the anti alopecia compoundcioteronel. Cioteronel is the common name forhexahydro-4-(5-methoxyheptyl)-2(1H)-pentalenone. It is also known, or iscommercially available, as X-ANDRO™, CPC-10997, CYOCTOL™, and EXANDRO™.It is a clear, colorless oil, soluble in lipid and relatively non-polarsolvents. Its preparation is disclosed in Kasha, W. J., PCT Int'l PatentApplication 83/04,019 (1983) 101 Chem. Abstr. 23037k (1984).

[0047] Its use is disclosed in U.S. Pat. No. 4,689,345. Its inhibitionof DHT binding in vitro is disclosed in Rec. Adv. Chemotherapy (Proc.14^(th) Int'l Congr. Chemotherapy Antimicrob., Sect. 1) at 261-70 and273-74 (Univ. Tokyo Press, 1985). Its cutaneous metabolism and clinicalpharmacokinetics is disclosed in de Zeeuw et al., 7 Pharm. Res. 638(1990), Weichers et al., 65 Int. J. Pharm. 77 (1990).

[0048] Another testosterone blocker is progesterone, pregn-4-ene-3,20-dione (commercially available as CORLUTINA™, CORLUVITE™, CYCLOGETS™,GESTIRON™, GESTONE™, LIPOLUTIN™, LUTOCYCLIN M™, PROGESTIN™, CPprogesterone powder, etc . . . ). Progesterone is insoluble in water andsoluble in alcohol, acetone, dioxane, and concentrated sulfuric acid. Itis sparingly soluble in vegetable oils. Its isolation, structure andbiological activity is described at length in Bardin et al. (eds.),Progesterone and Progestins (Raven Press, New York 1982). I prefer touse progesterone as the sole testosterone blocker.

[0049] Carrier Vehicles

[0050] The penetration enhancer and the vascular toner or testosteroneblocker, or both, may be mixed with a carrier vehicle. You can use avariety of vehicles to make my invention. The vehicle is simply acosmetically safe, medically safe solvent for the active ingredients.The vehicle should not adversely and significantly chemically react withthe active ingredients.

[0051] For example, propylene glycol, water and isopropyl alcohol may beused as vehicles. These may be used alone or in combination.

[0052] The vehicle can optionally provide functions in addition tosimply dissolving the active ingredients. For example, one can use amoisturizing vehicle, or a vehicle containing sunscreen. For amoisturizing or moisture retaining vehicle, one can use a vehicle madefrom a combination of (ranked in order of quantity used) water, mineraloil, petrolatum, lanolin, sorbitol solution, stearic acid, lanolinalcohol, cetyl alcohol, glyceryl stearate/PEG-`100 stearate,triethanolamine, dimethicone, propylene glycol, tri(PPG-3 myristylether) citrate, disodium EDTA, methylparaben, ethylparaben,propylparaben, fragrance, xanthan gum, butylparaben, and methyldibromoglutaronitrile.

[0053] It may be desirable to use a vehicle containing one or moresunscreens. This is because my preparations are used on the tops ofbalding scalps. Balding scalps are often largely unprotected from sundamage, as the user may not wear headgear and the balding scalp lacksthe sun shielding dense hair layer present on a healthy scalp. Addingsunscreen thus can protect the scalp from possible sun damage.Sunscreens, and vehicles containing sunscreen compounds, are widelyknown in the art. See, e.g., U.S. Pat. No. 4,522,807.

[0054] Other cosmetic vehicles are widely known in the art. I prefer touse VEHICLE/N™ as the vehicle. I prefer to use VEHICLE/N (TM) because ithas a cosmetically attractive “feel” to the user. Vehicle/N (TM) iscommercially available from the Neutrogena Dermatologics division ofJohnson & Johnson, Inc., New Brunswick, N.J. It is currently availablein two formulations, regular and mild. They are both versatile liquidvehicles for extemporaneous compounding of topical drugs. Bothformulations solublize selected dermatological agents and provideastringent and drying actions.

[0055] The VEHICLE/N (TM) ingredients are SD alcohol 40 (45%), purifiedwater (<45%), laureth-4 (>4%), isopropyl alcohol (4%) and propyleneglycol (<4%). The VEHICLE/N (TM) mild ingredients are purified water(>37.5%), SD alcohol-40 (37.5%), isopropyl alcohol (5%) and laureth-4(<5%). To compound with VEHICLE/N, add the appropriate quantity ofactive ingredient to yield the intended concentration.

[0056] VEHICLE/N (TM) is available as 50 mL of vehicle in a plasticbottle with applicator top. The bottle is filled only to ¾ capacity, toensure proper mixing. For 50 mL of VEHICLE/N, use the following amounts:Desired 0.1% 0.2% 0.5% 1.0% Concentration Bulk Active 50 mg 100 mg 250mg 500 mg Tablets 1 × 250 mg 4 × 150 mg 1.2% soln Desired 2.0% 3.0% 4.0%5.0% Concentration Bulk Active 1.0 gm 1.5 gm 2.0 gm 2.5 gm

[0057] For fastest dissolution, when tablets are used, crush them to apowder and then add the powder to the vehicle. When capsules are used,add the capsule contents only to the vehicle, and discard the capsuleshell. Shake the mixture gently. Most capsule contents and bulk activeingredients will dissolve within minutes, though some may take longer.

[0058] VEHICLE/N™ is available in a bottle with an APPLIDERM (TM)applicator top. The APPLIDERM (TM) applicator unit automatically filtersthe compounded mixture and provides a convenient, spill-proof,self-contained unit for topical application. To use the APPLIDERM (TM)applicator unit, push the applicator firmly into the bottle using thewhite cap as a holder. Screw the cap all the way down to seat theapplicator. Shake well. If tablets are dissolved in the vehicle, thenthe user should be instructed to allow the solution to stand overnightand to shake vigorously before the first use. VEHICLE/N (TM) should notbe used near fire or open flame due to alcohol content. Both VEHICLE/N(TM) and VEHICLE/N (TM) mild contain substantial alcohol and are notsuitable for use in acute dermatoses. Stinging may be noted if used onirritated or abraded skin. Avoid contact with eyes or eyelids. If theproduct accidentally comes in contact with eyes, rinse thoroughly withwater and contact physician. Keep out of reach of children. VEHICLE/N(TM) and VEHICLE/N (TM) mild are contraindicated in persons who haveshown hypersensitivity to any of the listed ingredients.

[0059] Preferred Formulations

[0060] Given a constant amount of testosterone blocker or vasculartoner, I have found that lower concentrations of penetration enhancercan decrease the efficacy of the final formulation, while higherconcentrations of penetration enhancer increase the risk of adverse sideeffects due to systemic penetration of the other active ingredient(s).

[0061] Similarly, you may use different testosterone blockers for thesame effect, and may use more or less of it. Using more testosteroneblocker allows one to use relatively less penetration enhancer, or aweaker enhancer. Titration of the two components against one another isa conventional technique well known in the art of pharmaceutical andcosmetics formulation. Such techniques are already used to titrateformulations for the wide variety of trans-dermal drugs and cosmeticscurrently available.

[0062] For example, in a four ounce quantity of liquid containing 5drops of trimethyl acetate, I prefer to use one percent (by volume) ofsoluble progesterone (U.S.P.).

[0063] A preferred formulation is: Minoxidil 1.0 gm bulk powder Solubleprogesterone (U.S.P.) 0.5 gm Trimethyl acetate 5 drops Vehicle N ( ™) 50mL

[0064] The following preparation is acceptable, and within the scope ofthe claims, but I do not prefer it: Minoxidil 1.0 gm bulk powder Solubleprogesterone (U.S.P.) 0.5 gm Methyl acetate 5 drops Vehicle N ( ™) 50 mL

[0065] Alternatively, an ethyl alcohol—water—propylene glycol solutionmay be used as the diluents and vehicle. For 100 mL of this formulation,use: ethyl alcohol 95% 75.5 cc purified water 18.5 cc propylene glycol6.0 cc progesterone 1.5 gm minoxidil 2.0-5.0 gm methyl acetate 5.0 gtts

[0066] These are my preferred formulations. These may be varied asdesired, but it is necessary to watch for unwanted side effects possiblydue to unwanted systemic penetration of the active ingredient(s). Forexample, minoxidil is pharmaceutically and cosmetically effectivetopically at anywhere from about 0.01 grams to about 50 grams per fourounces, depending on the frequency of topical administration.Testosterone blockers are also pharmaceutically and cosmeticallyeffective topically at anywhere from about 0.01 grams to about 50 gramsper four ounces, depending on the frequency of topical administration.With the higher concentrations, however, increasing the amount ofpenetration enhancer creates a greater risk of adverse side effects.

[0067] Summary

[0068] I have discussed several different specific formulas. T havefound these most useful. One can, however, vary the constituents toachieve the same effect without having a substantially differentproduct. For example, one can use a different testosterone blocker, or aweaker penetration enhancer in a higher concentration. Thus, the legalscope of my patent is not limited to the specific examples I discussherein; rather, the legal coverage of this patent is defined by theappended claims and their equivalents.

1. A composition of matter intended for topical use in preventing ortreating alopecia, or maintaining healthy hair, said composition ofmatter comprising: a. minoxidil; b. progesterone; and c. trimethylacetate in a concentration sufficient to aid said minoxidil and saidprogesterone in penetrating the skin surface to a depth of approximatelythe depth of hair bulbs:
 2. A method for preventing or treatingalopecia, or maintaining healthy hair, said method comprising topicallyadministering a mixture of: a. minoxidil; b. progesterone; and c.trimethyl acetate.